Autologous Airway Basal Cell Transplantation Alleviates Airway Epithelium Defect in Recurrent Benign Tracheal Stenosis.

BACKGROUND: Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis. METHODS: An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks. RESULTS: Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells. CONCLUSIONS: Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis.

Abnormal neutrophil polarization in chronic obstructive pulmonary disease and how cigarette smoke extracts attract neutrophils.

Background: Airway inflammation produced by neutrophils is a critical factor in the development of chronic obstructive pulmonary disease (COPD). Poor or excessive neutrophil polarization and chemotaxis may lead to pathogen accumulation and tissue damage. However, it is unclear how cigarette smoke extract (CSE) attracts neutrophils and to what extent COPD is affected by the improper polarization of these abnormal neutrophils. This study sought to assess the polarization and migration dynamics of neutrophils isolated from patients with different severities of COPD compared to healthy smoking and non-smoking control subjects, and to detect how CSE triggers the polarization of neutrophils. Methods: The neutrophils were freshly isolated using standard isolation protocol. The polarization of the neutrophils was observed using a Zigmond chamber when stimulated by a linear concentration gradient of CSE or N-formyl-methionine-leucine-phenylalanine (fMLP). Confocal laser-scanning microscopy was used to observe the intracellular calcium of the neutrophils. The experimental data are presented as the mean ± standard deviation. SPSS 20.0 software was used for the statistical analysis. A P value <0.05 was considered statistically significant. Results: The neutrophils from the COPD patients showed a higher frequency of spontaneous polarization and a lower prevalence of directionality polarization than those from the healthy control (HC) and smoker subjects. The abnormal polarization of the neutrophils from the COPD patients was altered by the influence of store-operated calcium entry (SOCE) component matrix interaction molecules 1 and 2 and calcium release-activated calcium channel protein 1 [stromal interaction molecule 1 (STIM1), Stromal interaction molecule 2 (STIM2), and calcium release-activated calcium modulator 1 (ORAI1)]. Conclusions: The COPD neutrophils exhibited unique polarization and migration patterns compared to those of the cells examined from other populations. The attraction of CSEs to neutrophils was mediated by the SOCE/Akt/Src pathway.

GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity.

The prevalence of non-obese nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with unclear etiology and pathogenesis. Here, we show GP73, a Golgi protein upregulated in livers from patients with a variety of liver diseases, exhibits Rab GTPase-activating protein (GAP) activity regulating ApoB export. Upon regular-diet feeding, liver-GP73-high mice display non-obese NAFLD phenotype, characterized by reduced body weight, intrahepatic lipid accumulation, and gradual insulin resistance development, none of which can be recapitulated in liver-GAP inactive GP73-high mice. Common and specific gene expression signatures associated with GP73-induced non-obese NAFLD and high-fat diet (HFD)-induced obese NAFLD are revealed. Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD. GP73 is pathologically elevated in NAFLD individuals without obesity, and GP73 blockade improves whole-body metabolism in non-obese NAFLD mouse model. These findings reveal a pathophysiological role of GP73 in triggering non-obese NAFLD and may offer an opportunity for clinical intervention.

Occurrence and dietary exposure assessment of pentachlorophenol in livestock, poultry, and aquatic foods marketed in Guangdong Province, China: Based on food monitoring data from 2015 to 2018.

As a persistent organic pollutant, pentachlorophenol (PCP) has serious impacts on human health. However, its presence in animal source food products sold in the Guangdong Province (GD) of China, and the resultant dietary exposure have not been elucidated. To address this gap, 3,100 samples from seven food categories, including beef, pork, mutton, offals, broilers, hen eggs, and farmed freshwater fish, marketed throughout four geographical regions of GD, were collected from 2015 to 2018. Gas chromatography coupled with mass spectrometry was employed to detect PCP levels in these food matrices. PCP was found in all food categories, but the average contamination levels were low, ranging from 0.40 µg/kg wet weight (ww) (hen eggs) to 5.85 µg/kg ww (offals). However, higher concentrations of PCP were detected (P < 0.05) in animal source food from the North region. Additionally, a temporal declining trend was observed in this four-year consecutive survey. The estimated human dietary exposure of PCP to population groups, including the general population and subgroups (male and female, children, and adults), was found to be far below the permissible daily intake (3 µg/kg body weight). Therefore, the health impacts of PCP should be correspondingly low for local residents, based on current toxicological knowledge. Regional exposure patterns varied due to different extents of contamination in the four areas, and pork, broilers, and freshwater fish were the major sources of dietary PCP exposure. PRACTICAL APPLICATION: As a persistent organic pollutant, pentachlorophenol (PCP) has serious impacts on human health. However, its presence in animal source food products sold in Guangdong Province of China, and the resultant dietary exposure have not been elucidated. In this study, we conducted an in-depth investigation on the occurrence of PCP in major foodstuff categories, including beef, pork, mutton, broilers, offals, hen eggs, and farmed freshwater fish, marketed in all 21 prefecture-level divisions of Guangdong Province, in order to provide integral insights for regulatory authorities.

Hepatitis B virus large surface protein in serum as a candidate biomarker for evaluating hepatitis B virus infection.

AIM: To develop a sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of serum hepatitis B virus large surface protein (HBV-LP), and study the clinical value of HBV-LP. METHODS: Serum HBV-LP levels and a panel of other HBV markers were investigated in a large population of patients with chronic HBV. The clinical value of HBV-LP was evaluated by comparing the coincidence of detection of HBV markers and the change of serum HBV-LP level during antiviral therapy. RESULTS: The ELISA was found to be sensitive and specific for the detection of HBV-LP. Serum HBV-LP level was positively correlated with HBV DNA (r=0.743) in HBV patients. Among the five HBV markers tested, HBV-LP displayed the highest coincidence rate (94.7%) with HBV DNA. CONCLUSIONS: Serum HBV-LP was strongly correlated with HBV DNA. This ELISA therefore offers a promising approach for the diagnosis and treatment monitoring of HBV patients.